Primary open angle glaucoma (POAG) is one of the leading causes of blindness in the elderly population worldwide. Slowing or preventing the progression of this disease is an urgent public health goal. We hypothesize that biomarkers exist in the blood of individuals susceptible to developing POAG that will allow identification of those at risk prior to clinical evidence of the disease. A case-control pilot study is proposed to test the hypothesis that plasma contains diagnostic biomarkers for POAG. Plasma will be collected from clinically documented patients from the United States in four study groups, including a control group and three POAG groups (ocular hypertension, possible POAG and definite POAG). ELISA will be used to screen plasma for protein oxidative modifications that may serve as POAG plasma biomarkers. High resolution MALDI TOF TOF and QTOF mass spectrometry will be used to screen plasma for proteomic patterns and/or to determine the sequence of POAG diagnostic plasma peptides. The long term goal is the development of routine diagnostic technology for use in clinical medicine to predict POAG susceptibility and to monitor therapeutic efficacy, essentially as serum cholesterol measurements are used today for risk management for cardiovascular disease. This research will lead to methods for early detection of "POAG at risk" individuals, new methods for measuring POAG therapeutic efficacies and new insights into mechanisms of glaucoma pathology. PUBLIC HEALTH RELEVANCE: Primary open angle glaucoma (POAG) is the most common form of glaucoma and affects about 3 million Americans and over 70 million people worldwide. Slowing or preventing the progression of this disease is an urgent public health goal. The proposed research will lead to methods for early detection of "POAG at risk" individuals, new methods for measuring POAG therapeutic efficacies and new insights into the mechanisms of glaucoma pathology.